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MJFF invests $5 million in Vandy-BMS Parkinsonís collaboration
November 2012
by Lori Lesko  |  Email the author
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NASHVILLE, Tenn.óA $5 million investment from the Michael J. Fox Foundation (MJFF) has helped launch a major collaboration between the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) and global biopharmaceutical company Bristol-Myers Squibb Co. (BMS) that aims to develop a first-in-class symptomatic treatment for Parkinson's disease.

Under the terms of the agreement, announced Sept. 21, Vanderbilt University will receive an upfront payment and three-year research funding to continue to discover additional compounds, while BMS will have the right to develop and commercialize products resulting from the collaborative research program. Vanderbilt is also eligible to receive milestones and royalties based on developmental success and worldwide sales of the drugs emerging from the collaboration.

If all milestones are met, the Vanderbilt team, led by VCNDD Director P. Jeffrey Conn, is hopeful that an experimental drug could enter clinical testing as soon as 2013.

"The long-term commitment of, and collaboration with, MJFF has been critical to advancing this program to the stage where it is nowóperfectly positioned to work closely with Bristol-Myers Squibb for further development," said Conn in a news release. "Partnering with Bristol-Myers Squibb is a real win for Vanderbilt and for Parkinson's patients."

An estimated 1 million Americans have Parkinson's disease, a progressive brain disorder characterized by resting tremors, rigidity and slowness of movement, according to the U.S. National Institutes of Health (NIH). Parkinson's is caused by the death of nerve cells in a specific brain region that produce the neurotransmitter dopamine.

Founded and led by popular actor Michael J. Fox, MJFF has partnered with Conn and his team at Vanderbilt since 2005 in pursuit of a new class of Parkinson's drugs targeting the neurotransmitter glutamate. By bypassing the dopamine system altogether, a glutamate-based treatment could provide the same symptomatic benefits of levodopa while avoiding disabling side effects such as dyskinesia (uncontrollable movement). The Vanderbilt team has focused on a specific glutamate receptor called mGluR4.

The mGluR4 receptors are highly expressed in areas of the brain directly relevant to Parkinson's disease, Conn says. mGluR4 PAMs represent an approach to correct the dysregulated signaling observed in Parkinson's disease and pharmacologically mimic a surgical procedure that has been successful in alleviating symptoms of Parkinson's disease.

To minimize the likelihood of side effects, the drugs must take a subtle approach to manipulating the mGluR4 receptor.

"You can liken it to a dimmer switch on a light in your home, where you can turn up the gain of the receptor and its activity, or turn it down without completely activating it or shutting it off," Conn said in a 2009 interview.

Even if the mGluR4I receptor theory is shown to be correct, "I would not consider this a possible 'cure,'" Conn tells ddn. "The hope is that mGluR4 PAMs could reduce symptoms of Parkinson's disease. The ultimate outcome cannot be predicted at this stage, but will only be known after completion of clinical studies. Our hope is that this will be a major step towards treating Parkinson's symptoms."

Although MJFF's direct funding of the research has ended and the organization will not play a direct role in the ongoing research, "they are highly supportive and have expressed an eagerness to provide insights and help as the program moves forward," notes Conn.
 
Unlike the traditional steps of research and development and funding a breakthrough drug, MJFF adheres to an aggressively funded research agenda that ensures the development of improved therapies for those living with Parkinson's today. From its inception, MJFF has invested in high-risk, high-reward research targetsóan approach that in the last decade has transformed the broader approach in the Parkinson's disease research field, according to MJFF CEO Todd Sherer.

The Vanderbilt and BMS collaborative agreement is "the latest example of how de-risking speeds promising treatments toward clinical testing and patients," Sherer says. De-risking is the foundation's strategy to make research investments that build a compelling scientific case for the most promising new approaches to Parkinson's disease, he explains.

"This, in turn, builds the business case for further investment by funders with the resources to carry the work forward through the most expensive stages of clinical development and regulatory approval," Sherer says.


 
Code: E111223

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